Diseases of aging present an overwhelming burden on health care resources, with an estimated 100 billion dollars in annual U.S. expenditures and a population of four million Alzheimer's disease (AD) patients. While AD refers to full syndrome expression of cognitive decline, a major research focus has emerged to identify patients with early focused memory difficulties, or amnestic mild cognitive impairment (aMCI). Early disease identification has implications for health care utilization throughout the disease course and provides an important window for early therapeutic treatment, a major research aim recently stressed by the Food and Drug Administration. Several converging lines of evidence suggest that augmenting the somatotropic axis (growth hormone (GH) and insulin-like growth factor 1 (IGF-1)), that declines across the life span, may ameliorate the cognitive and physiological declines that occur during aging. Our recent six-month double-blind treatment trial, treatment with one such novel agent, growth hormone releasing hormone (GHRH), resulted in specific gains in working memory and psychomotor processing speed in healthy aging adults. The extension of that work, our recently funded trial (Vitiello PI, AG025515) utilizes an improved GHRH formulation to evaluate comprehensive neurocognitive changes in both healthy aged and aMCI subjects. The behavioral improvements stemming from GHRH are likely related to the wide-ranging neurotrophic, neuroprotective, and cerebrovascular effects associated with IGF-1 demonstrated in animal studies. However, it remains unknown whether GHRH induces cellular changes in human subjects with aMCI. This proposed project seeks fill this knowledge gap. Because NAA decreases across the life span, with further decreases observed in MCI that predict conversion to AD, treatments that specifically slow or reverse NAA decline may have important behavioral consequences that can be examined in this linked trial. PUBLIC HEALTH RELEVANCE: This project seeks to evaluate whether brain N-acetyl aspartate (NAA) can be altered by growth hormone releasing hormone (GHRH) treatment in individuals with mild cognitive impairment (aMCI).